INCONTINENTIA PIGMENTI
DNA ANALYSIS

Familial Incontinentia Pigmenti is an X-linked disorder that affects the development of several ectodermal derivatives, skin, hair, teeth, nails, brain, and eyes. This disorder is almost always lethal in males. The prominent skin findings occur in four classic stages: perinatal inflammatory vesicles, verrucous patches, a distinctive linear pattern of hyper-pigmentation, and finally dermal scarring. The disturbances in the skin, sometimes a localized rash, sometimes widely distributed eruptions of vesicles, is usually seen in the newborn period and heals completely by two or three years of age. The resulting pigmentation and scarring tend to fade after the teen years, but the loss of hair and hair follicles and the scarring and atrophy of the skin may persist lifelong. Associated findings include incomplete dentition (missing teeth and pointed teeth) and vascular abnormalities of the retina (similar to retinopathy of prematurity). Dystrophy of the nails is frequent but usually mild, and unilateral breast aplasia or breast asymmetry is a recognized but uncommon feature. Females affected with IP have an extremely skewed X-inactivation pattern, due to selective elimination of cells that express the mutant X-chromosome. The gene responsible for familial IP was recently identified as the NEMO gene (NF-kB Essential MOdulator) that maps to chromosome Xq28. NEMO is essential to activation of the NF-kB transcription factor, which participates in many immune, inflammatory, and apoptotic pathways. Different NEMO gene mutations have been identified. Approximately 80% of IP patients were shown to carry a common deletion mutation that removes exons 4 through 10 of the NEMO gene. This DNA rearrangement appears to be mediated by flanking repeat sequences. Our laboratory is currently offering diagnostic testing for the common NEMO gene deletion by Southern analysis.

Reasons for Referral:

Confirmation of diagnosis of Incontinentia Pigmenti for individuals with phenotypic features. Unusual phenotypes (such as IP in a male) should be discussed in advance.
Carrier testing and prenatal diagnosis in families with an identified deletion mutation in the NEMO gene.

Testing Methodology:

Southern analysis for the common NEMO gene deletion is performed with an exon 2 probe and a genomic HindIII restriction digest. This assay detects an 8kb deletion junction fragment and a normal 12kb band. This diagnostic strategy was designed to avoid potential complications due to the presence of a NEMO pseudogene downstream.

Sensitivity:

>99% detection of common deletion mutation when present. Approximately 80% of patients with IP have been found to carry the common NEMO gene deletion.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject, or their legal guardian, sign our consent form and submit it with the sample.

Turnaround Time:

3 weeks

CPT Codes and Prices:

Index: 83891, 83897, 83896, 83892, 83912

References:

1. The International Incontinentia Pigmenti (IP) Consortium. (2000) Nature 405: 466-472.